摘要
目的探讨丹参酚酸B(SA-B)抗肝纤维化作用机制。方法分离大鼠肝星状细胞(HSC),于无包被塑料培养皿中原代培养7天,继以10-6mmol/L SA-B孵育,再加10ng/ml的转化生长因子β1(TGF-β1)或血小板衍生生长因子-BB(PDGF-BB)刺激。以Western blot法观察SA-B对TGF-β1或PDGF-BB刺激的HSC内ERK蛋白及其磷酸化表达的影响及对TGF-β1或PDGF-BB刺激的HSC表面TGF-β1Ⅰ型受体(TβRⅠ)、Ⅱ型受体(TβRⅡ)或PDGF受体β(PDGFR-β)表达的影响。结果SA-B可抑制原代正常培养9天的HSC及TGF-β1刺激的HSC中ERK1/2的磷酸化;对正常培养的HSC和TGF-β1刺激的HSC表面TβRⅠ和TβRⅡ的表达无明显影响。SA-B抑制原代正常培养9天的HSC和经PDGF-BB刺激的HSC中PDGFR-β的表达,但对PDGF-BB刺激的HSC中ERK1/2磷酸化没有明显作用。结论SA-B抑制TGF-β1诱导的HSC内ERK信号传导通路。这一抑制作用与HSC上TβR的表达无关,也与PDGF-BB在HSC内的ERK信号传导通路无关。SA-B对PDGF-BB在HSC内的信号传导通路的抑制作用在于抑制了HSC上PDGF受体的表达。
Objective To explore the anti-hepatic fibrosis mechanisms of salvianolic acid B （SA-B）, Methods Hepatic stellate cells （HSCs） isolated from rats were primarily cultured in uncoated plastic culture dish for 7 days, then were incubated with 10^-6mmol/L SA-B and stimulated with 10 ng/ml transforming growth factor- β1（TGF-β1 ） or platelet-derived growth factor-BB （PDGF-BB）, Expressions of extracellular-regulated kinase （ERK） and its phosphorylation in HSC,and expressions of TGF β1 receptor Ⅰ （TβR Ⅰ ） and H （TβR Ⅱ ） and PDGF receptor β （PDGFR-β） on the surface of HSC induced by TGF-β1 or PDGF-BB were detected with Western blot assay. Results SA-B inhibited the phosphorylation of ERK1/2 in HSC primary normally cultivated for 9 days stimulated or un-stimulated by TGF-β1 , but could not affect the expressions of TβR I and TβR H on the HSC surface; it down-regulated the expression of PDGFR-β, but had no obvious effect on the phosphorylation of ERK1/2 in those HSC stimulated or un-stimulated by PDGF-BB. Conclusion SA-B inhibits the ERK signal transduction induced by TGF-β1 in HSC, which is independent of the expressions of TβR on HSC surface and also free from the ERK signal transduction stimulated by PDGF-BB. And its inhibition on PDGF-BB signal transduction in HSC is by way of restraining the expression of PDGFR in HSC.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2006年第5期439-442,共4页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金项目(No.30271657)
上海市重点学科建设项目资助(No.Y0302)
上海市教委重点学科建设项目资助
